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Portrait of Sara Snogerup Linse

Sara Linse


Portrait of Sara Snogerup Linse

alpha-Lactalbumin unfolding is not sufficient to cause apoptosis, but is required for the conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells).


  • Malin Svensson
  • Jonas Fast
  • Anki Mossberg
  • Caroline Düringer
  • Lotta Gustafsson
  • Oskar Hallgren
  • Charles L. Brooks
  • Lawrence Berliner
  • Sara Linse
  • Catharina Svanborg

Summary, in English

HAMLET (human -lactalbumin made lethal to tumor cells) is a complex of human -lactalbumin and oleic acid (C18:1:9 cis) that kills tumor cells by an apoptosis-like mechanism. Previous studies have shown that a conformational change is required to form HAMLET from -lactalbumin, and that a partially unfolded conformation is maintained in the HAMLET complex. This study examined if unfolding of -lactalbumin is sufficient to induce cell death. We used the bovine -lactalbumin Ca2+ site mutant D87A, which is unable to bind Ca2+, and thus remains partially unfolded regardless of solvent conditions. The D87A mutant protein was found to be inactive in the apoptosis assay, but could readily be converted to a HAMLET-like complex in the presence of oleic acid. BAMLET (bovine -lactalbumin made lethal to tumor cells) and D87A-BAMLET complexes were both able to kill tumor cells. This activity was independent of the Ca2+site, as HAMLET maintained a high affinity for Ca2+ but D87A-BAMLET was active with no Ca2+ bound. We conclude that partial unfolding of -lactalbumin is necessary but not sufficient to trigger cell death, and that the activity of HAMLET is defined both by the protein and the lipid cofactor. Furthermore, a functional Ca2+-binding site is not required for conversion of -lactalbumin to the active complex or to cause cell death. This suggests that the lipid cofactor stabilizes the altered fold without interfering with the Ca2+site.


  • Division of Microbiology, Immunology and Glycobiology - MIG
  • Biophysical Chemistry
  • Respiratory Medicine, Allergology, and Palliative Medicine

Publishing year







Protein Science





Document type

Journal article


The Protein Society


  • Immunology in the medical area
  • Microbiology in the medical area




  • ISSN: 1469-896X